Research Abstracts Online
January 2009 - March 2010

University of Minnesota Twin Cities
Medical School
Department
of Pharmacology

PI: Kirill Martemyanov

Molecular Basis of RGS Protein Function in the Striatum

G protein signaling pathways in the striatum mediate a range of critical neuronal processes that control behavior, locomotion, and pain perception and underlie drug abuse and addiction. The normal functioning of these pathways is hinged on the tight control of signal duration mediated by the regulators of G protein signaling (RGS) proteins. The long-term goal of this research group is to elucidate the mechanisms governing the function of RGS proteins in neurons as a necessary prerequisite to understanding neurological disease processes and therapeutic means of their treatment. The main focus of this study is on RGS9-2, a striatum specific regulator that crucially controls signaling efficiency through dopamine and opioid receptor systems, which are exploited by drugs of abuse. However, the molecular mechanisms of RGS9-2 function are largely unknown and need to be elucidated for better understanding of the neurochemical basis of addiction. To this end, these researchers have recently discovered that RGS9-2 in the striatum exists in a complex with a novel neuronal protein, which they named R7 Binding Protein (R7BP). Preliminary data suggest that R7BP serves as a critical modulator of RGS9-2 function in neurons.

The researchers are using MSI resources for the following specific aims: to determine the mechanisms mediating stability and localization of RGS9-2; to understand the role of R7BP in the regulation of RGS9-2 catalytic activity; and to further characterize the molecular composition of the G protein inactivating complex in striatal neurons. These studies should provide an understanding of the regulation of signaling in the striatum and generate insights into the molecular mechanisms of G protein signal disruption caused by drug abuse and neurological diseases.